Abstract
Chemotherapy is an emerging effective treatment for cancer. However, one of the reasons why chemotherapy has a limited therapeutic effect in bladder cancer is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that sensitive to high concentrations of glutathione and near-infrared laser irradiation, which increases the drug accumulation at the tumor site and combines chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment.Methods: The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and photothermal effect of NPs were demonstrated. Therapeutic efficacy of NPs for bladder cancer was evaluated.Results: The DOX&IR780@PEG-PCL-SS NPs we synthesized use internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes in nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drug from the nanoparticles, producing a photothermal effect and further killing the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of drugs in tumor cells. The mice in the experimental group can be found to have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by small animal imaging and have good imaging results, to facilitate our assessment during the experiment.Conclusion: A dual sensitivity to glutathione and near-infrared laser irradiation. Long-circulating nanoparticle was developed for delivering IR780 and DOX, which could achieve NIR laser-controlled drug release and imaging guidance for chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases.
An internal cross-linked polymeric nanoparticle with dual sensitivity for combination therapy of muscle-invasive bladder cancer